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The Journal of Physical Chemistry. B Jul 2024Macroions such as nanoparticles, polyelectrolytes, ionic gels, and amphiphiles can form condensed, often self-assembled, phases that are embedded in a solvent region....
Macroions such as nanoparticles, polyelectrolytes, ionic gels, and amphiphiles can form condensed, often self-assembled, phases that are embedded in a solvent region. The condensed phase contains not only the partially or fully immobile charges of their macroions but also corresponding counterions that are mobile and thus free to migrate out of their confinement into the solvent region where they benefit from high translational entropy. Based on the nonlinear Poisson-Boltzmann model for monovalent ions, we quantify the corresponding fraction of released counterions for a planar slab geometry of the macroion phase. Slab thickness, extension of the solvent phase, fixed background charge density provided by the macroions, and dielectric constants inside slab and solvent combine into three dimensionless parameters that the fraction of released counterions depends on. We calculate that fraction and analyze the limits of a thin macroion phase, a large solvent phase, and linearized theory, where simple analytic results become available. Of particular interest is the presence of a single-planar interface that separates a bulk macroion phase from an extended solvent region. We calculate the apparent surface charge density that emerges due to the released counterions. Our model yields a comprehensive description of counterion partitioning between a planar macroion phase and a solvent region on the level of mean-field electrostatics in the absence of added salt ions.
PubMed: 38958595
DOI: 10.1021/acs.jpcb.4c03222 -
Journal of Chemical Theory and... Jul 2024Self-splicing ribozymes are small ribonucleic acid (RNA) enzymes that catalyze their own cleavage through a transphosphoesterification reaction. While this process is...
Self-splicing ribozymes are small ribonucleic acid (RNA) enzymes that catalyze their own cleavage through a transphosphoesterification reaction. While this process is involved in some specific steps of viral RNA replication and splicing, it is also of importance in the context of the (putative) first autocatalytic RNA-based systems that could have preceded the emergence of modern life. The uncatalyzed phosphoester bond formation is thermodynamically very unfavorable, and many experimental studies have focused on understanding the molecular features of catalysis in these ribozymes. However, chemical reaction paths are short-lived and not easily characterized by experimental approaches, so molecular simulation approaches appear as an ideal tool to unveil the molecular details of the reaction. Here, we focus on the model hairpin ribozyme. We show that identifying a relevant initial conformation for reactivity studies, which is frequently overlooked in mixed quantum-classical studies that predominantly concentrate on the chemical reaction itself, can be highly challenging. These challenges stem from limitations in both available experimental structures (which are chemically altered to prevent self-cleavage) and the accuracy of force fields, together with the necessity for comprehensive sampling. We show that molecular dynamics simulations, combined with extensive conformational phase space exploration with Hamiltonian replica-exchange simulations, enable us to characterize the relevant conformational basins of the minimal hairpin ribozyme in the ligated state prior to self-cleavage. We find that what is usually considered a canonical reactive conformation with active site geometries and hydrogen-bond patterns that are optimal for the addition-elimination reaction with general acid/general base catalysis is metastable and only marginally populated. The thermodynamically stable conformation appears to be consistent with the expectations of a mechanism that does not require the direct participation of ribozyme residues in the reaction. While these observations may suffer from forcefield inaccuracies, all investigated forcefields lead to the same conclusions upon proper sampling, contrasting with previous investigations on shorter timescales suggesting that at least one reparametrization of the Amber99 forcefield allowed to stabilize aligned active site conformations. Our study demonstrates that identifying the most pertinent reactant state conformation holds equal importance alongside the accurate determination of the thermodynamics and kinetics of the chemical steps of the reaction.
PubMed: 38958594
DOI: 10.1021/acs.jctc.4c00294 -
Nutrition in Clinical Practice :... Jul 2024Many patients and family caregivers have informational needs, especially regarding gastrostomy care and home gastrostomy tube feeding. YouTube is a potential accessible...
BACKGROUND
Many patients and family caregivers have informational needs, especially regarding gastrostomy care and home gastrostomy tube feeding. YouTube is a potential accessible option for educational resources concerning these topics.
METHODS
This study aimed to explore the educational quality and content of informational YouTube videos. We used "gastrostomy," "G-tube," "enteral feeding," and "enteral nutrition," as search keywords on YouTube on October 3, 2021. A total of 229 videos were evaluated using the global quality scale (GQS) and modified DISCERN scoring system. Variables extracted from the videos included general features, video parameters, and content themes.
RESULTS
The GQS and modified DISCERN scores were 3.31 ± 0.90 and 2.63 ± 1.23, respectively. There were educational quality and differences among videos uploaded by various agencies. Frequent video content themes included "cleaning and dressing a gastrostomy tube," "bolus method," and "replacing a balloon-type of gastrostomy tube."
CONCLUSION
Results showed that YouTube can be a supplemental educational resource for people requiring gastrostomy care and for their caregivers. However, given the open-access nature of YouTube, healthcare professionals' guidance is needed for video selection. Healthcare professionals should know and use specific, reliable resources to effectively guide and educate patients with gastrostomy and their caregivers, enhancing their self-management skills and knowledge.
PubMed: 38958580
DOI: 10.1002/ncp.11186 -
American Journal of Physical Medicine &... Jul 2024To examine whether inpatient rehabilitation facility (IRF) patients' risk-adjusted functional outcomes varied with five social drivers of health: Medicare-Medicaid dual...
Do Medicare Inpatient Rehabilitation Facility Patients' Self-Care and Mobility Outcomes Vary by Dual Eligibility Status, Race and Ethnicity, Rural Residence, Socioeconomic Status, and Living Alone?
OBJECTIVE
To examine whether inpatient rehabilitation facility (IRF) patients' risk-adjusted functional outcomes varied with five social drivers of health: Medicare-Medicaid dual eligibility status, race and ethnicity, rural residence, socioeconomic status (SES), and living alone.
DESIGN
This cohort study examined unadjusted and adjusted mobility and self-care change scores during IRF stays for 428,710 Medicare patients with and without social drivers of health. Regression models isolated the mean marginal effect of each of the five social factors on mobility and self-care change scores after adjusting for covariates.
RESULTS
Patients with full dual status had slightly lower risk-adjusted mobility and self-care improvement (-4.5% and -3.3%, respectively) compared to patients without dual status. Patients who identified as Black, Asian and Native Hawaiian had self-care marginal effects that were slightly lower (-4.8%, -4.1% and -3.7%, respectively) than patients who were White. Patients living in lower SES neighborhoods and patients who lived alone had slightly higher mobility and self-care improvement scores. Risk-adjusted marginal differences in improvement scores for patients with and without these social factors were small and did not meet the meaningfully different criteria.
CONCLUSIONS
Overall, IRF patients' risk-adjusted functional outcomes did not vary meaningfully by dual eligibility status, race or ethnicity, rural residence, SES or living alone.
PubMed: 38958576
DOI: 10.1097/PHM.0000000000002568 -
The Contribution of Shame to Eating Disorder Treatment Outcomes in a Community Mental Health Clinic.The International Journal of Eating... Jul 2024Shame is a powerful self-conscious emotion that is often experienced by individuals with eating disorders (EDs). While the association between EDs and shame is...
OBJECTIVE
Shame is a powerful self-conscious emotion that is often experienced by individuals with eating disorders (EDs). While the association between EDs and shame is well-established, there is limited research investigating the contribution of pre-treatment shame to clinical outcomes.
METHOD
Participants (N = 273) received outpatient cognitive-behavioral therapy for eating disorders (CBT-ED). We investigated pre-treatment shame as a predictor of dropout and as a moderator of change in ED psychopathology and clinical impairment from pre-treatment to post-treatment. We also explored the potentially moderating roles of body mass index, ED diagnostic category, and co-occurring anxiety and depression diagnoses.
RESULTS
Shame improved substantially (d = 1.28) despite not being explicitly targeted in treatment. Pre-treatment shame did not predict treatment dropout. Individuals high in shame started and ended treatment with higher ED symptoms and impairment than those with low shame. The contribution of pre-treatment shame on the degree of change in symptoms/impairment depended critically on whether analyses controlled for pre-treatment symptoms/impairment. When those were controlled, high pre-treatment shame was associated with substantially less improvement in ED symptoms and impairment. There was some evidence that ED diagnosis and co-occurring depressive diagnoses may moderate the relationship between shame and treatment outcome. Changes in shame were positively associated with changes in ED symptoms and clinical impairment.
DISCUSSION
A high level of shame at pre-treatment is not a contraindication for CBT-ED as good therapeutic outcomes can be achieved. However, outcomes may be enhanced among individuals high in shame by offering adjunctive interventions that explicitly target shame.
PubMed: 38958544
DOI: 10.1002/eat.24248 -
ACS Sensors Jul 2024Near-infrared (NIR) heptamethine cyanine (HCy) dyes are promising photothermal transducers for image-guided cancer treatment owing to their prominent photophysical...
Near-infrared (NIR) heptamethine cyanine (HCy) dyes are promising photothermal transducers for image-guided cancer treatment owing to their prominent photophysical properties and high photothermal conversion ability. However, HCy photothermal transducers usually have poor photostability due to degradation induced by the self-generated reactive oxygen species. Herein, a novel mitochondria-targeting dimeric HCy dye, named dimeric oBHCy, is rationally designed, exhibiting strong near-infrared II (NIR-II) fluorescence emission, high photothermal conversion efficiency (PCE), and excellent photostability. The large π-conjugation and drastic intramolecular motion of the diphenol rotor in the dimeric oBHCy enhance the nonradiative energy dissipation and suppress the intersystem crossing process, thereby achieving a high PCE (49.2%) and improved photostability. Impressively, dimeric oBHCy can precisely target mitochondria and induce mitochondrial damage upon NIR light irradiation. Under the guidance of in vivo NIR-II fluorescence imaging, efficient NIR light-activated photothermal therapy of 4T1 breast tumors is accomplished with a tumor inhibitory rate of 96% following a single injection of the dimeric oBHCy. This work offers an innovative strategy for designing cyanine photothermal transducers with integrated NIR-II fluorescence and photothermal properties for efficient cancer theranostics.
PubMed: 38958530
DOI: 10.1021/acssensors.4c00561 -
Journal of Cellular Physiology Jul 2024Autophagy is a lysosome-mediated self-degradation process of central importance for cellular quality control. It also provides macromolecule building blocks and... (Review)
Review
Autophagy is a lysosome-mediated self-degradation process of central importance for cellular quality control. It also provides macromolecule building blocks and substrates for energy metabolism during nutrient or energy deficiency, which are the main stimuli for autophagy induction. However, like most biological processes, autophagy itself requires ATP, and there is an energy threshold for its initiation and execution. We here present the first comprehensive review of this often-overlooked aspect of autophagy research. The studies in which ATP deficiency suppressed autophagy in vitro and in vivo were classified according to the energy pathway involved (oxidative phosphorylation or glycolysis). A mechanistic insight was provided by pinpointing the critical ATP-consuming autophagic events, including transcription/translation/interaction of autophagy-related molecules, autophagosome formation/elongation, autophagosome fusion with the lysosome, and lysosome acidification. The significance of energy-dependent fine-tuning of autophagic response for preserving the cell homeostasis, and potential implications for the therapy of cancer, autoimmunity, metabolic disorders, and neurodegeneration are discussed.
PubMed: 38958520
DOI: 10.1002/jcp.31366 -
Advanced Science (Weinheim,... Jul 2024Resistive switching memories have garnered significant attention due to their high-density integration and rapid in-memory computing beyond von Neumann's architecture....
Resistive switching memories have garnered significant attention due to their high-density integration and rapid in-memory computing beyond von Neumann's architecture. However, significant challenges are posed in practical applications with respect to their manufacturing process complexity, a leakage current of high resistance state (HRS), and the sneak-path current problem that limits their scalability. Here, a mild-temperature thermal oxidation technique for the fabrication of low-power and ultra-steep memristor based on Ag/TiO/SnO/SnSe/Au architecture is developed. Benefiting from a self-assembled oxidation layer and the formation/rupture of oxygen vacancy conductive filaments, the device exhibits an exceptional threshold switching behavior with high switch ratio exceeding 10, low threshold voltage of ≈1 V, long-term retention of >10 s, an ultra-small subthreshold swing of 2.5 mV decade and high air-stability surpassing 4 months. By decreasing temperature, the device undergoes a transition from unipolar volatile to bipolar nonvolatile characteristics, elucidating the role of oxygen vacancies migration on the resistive switching process. Further, the 1T1R structure is established between a memristor and a 2H-MoTe transistor by the van der Waals (vdW) stacking approach, achieving the functionality of selector and multi-value memory with lower power consumption. This work provides a mild-thermal oxidation technology for the low-cost production of high-performance memristors toward future in-memory computing applications.
PubMed: 38958519
DOI: 10.1002/advs.202401915 -
The International Journal of Eating... Jul 2024Understanding the emotional context of feeding behavior may help identify causal mechanisms of food avoidance among individuals with anorexia nervosa. Although...
BACKGROUND
Understanding the emotional context of feeding behavior may help identify causal mechanisms of food avoidance among individuals with anorexia nervosa. Although predominant food avoidance models assume fear of fat drives feeding behavior, disgust may be more theoretically and proximally relevant to moment-to-moment experiences of feeding. This study, therefore, aimed to examine affect and food avoidance using automated affect analysis from facial response by measuring time-specific transitions in disgust during a laboratory eating paradigm. We hypothesized that phase transitions in disgust would distinguish temporally self-initiated eating from food avoidance.
METHODS
Sixty-three adolescents with anorexia nervosa or another low-weight eating disorder (LWED) and 27 age- and sex-matched controls were recruited as part of a larger study; 45 patients and 22 controls provided data on autonomous eating and facial affect during a laboratory meal. Dynamic structural equation models quantified moment-to-moment relationships between disgust and feeding behavior.
RESULTS
Self-initiated eating was associated with greater increases in disgust, but not fear, intensity among those with LWED relative to control participants and greater disgust intensity predicted lower likelihood of self-initiated eating.
DISCUSSION
Phasic transitions in disgust provide moment-to-moment evidence of affective influence on self-initiated eating and lend credibility to the hypothesis that disgust contributes to food avoidance and initiation in individuals with LWED.
PubMed: 38958505
DOI: 10.1002/eat.24254 -
The International Journal of Eating... Jul 2024Gay and bisexual men are at an increased risk for eating disorders (EDs) and muscle dysmorphia (MD) compared with their heterosexual counterparts. Existing...
OBJECTIVE
Gay and bisexual men are at an increased risk for eating disorders (EDs) and muscle dysmorphia (MD) compared with their heterosexual counterparts. Existing dissonance-based (DB) EDs prevention programs for this population have been evaluated in the United States; however, these programs have not been evaluated in the Brazilian context. Thus, we investigated the feasibility, acceptability, and efficacy of a DB ED prevention program (i.e., the PRIDE Body Project) among Brazilian cisgender gay and bisexual men.
METHOD
Eligible men were randomly assigned to either a DB intervention (n = 74) condition or an assessment-only control (AOC) condition (n = 75). Participants completed measures assessing ED and MD risk and protective factors at baseline, post-intervention, 1-month, 6-month, and 1-year follow-up. Those in the intervention condition also completed acceptability measures.
RESULTS
Feasibility and acceptability ratings were highly favorable. Regarding efficacy, post-intervention results were not significant, except for self-objectification, which showed a significantly greater decrease in the DB condition compared with the AOC condition at all time-points of follow-ups (Cohen's d = -0.31 to -0.76). At follow-up, the DB condition showed significantly greater decreases in appearance-ideal internalization, drive for muscularity, self-objectification, ED and MD symptoms at 1-month, 6-month, and 1-year follow-ups (d = -0.33 to -0.92) compared with the AOC condition. Significant increases were observed in the DB compared with the AOC condition for body appreciation at 1-month, 6-month, and 1-year follow-ups (d = 0.31-0.81).
DISCUSSION
Results support the feasibility, acceptability, and efficacy of the PRIDE Body Project up to 1-year in Brazilian cisgender gay and bisexual men.
TRIAL REGISTRATION
Brazilian Registry of Clinical Trials (ReBEC; available at http://www.ensaiosclinicos.gov.br/) number of registration: RBR-62fctqz.
PubMed: 38958485
DOI: 10.1002/eat.24246